New-onset refractory status epilepticus: A retrospective cohort study

Abstract

To describe the clinical, laboratory, neuroimaging, electroencephalographic features, etiology, treatment, as well as short-term and long-term outcomes of adults with new-onset refractory status epilepticus (NORSE). Method: A retrospective, single institution cohort study (2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018) of consecutive adult patients with NORSE. Results: Among 20 patients with NORSE, nine (45 %) had prodromal febrile illness, 12 (60 %) had evidence of inflammation on CSF profile. Six patients (30 %) met criteria for definite autoimmune encephalitis (AE) while 8 patients (40 %) had probable AE. Eleven out of 13 (85 %) patients had an abnormal FDG-PET scan with the most common finding being regional hypermetabolism. Fourteen patients (70 %) received immunotherapy and ten (50 %) received the ketogenic diet (KD). Fifteen patients (75 %) progressed to super-refractory status epilepticus (SRSE) and seven patients (35 %) died in the hospital or within six months of discharge. Among the surviving patients, eight (40 %) had a good outcome (i.e., modified Rankin Scale score 0-2); 12 (80 %) received a diagnosis of epilepsy of which nine (75 %) developed drug-resistant epilepsy. Conclusions: New-onset refractory status epilepticus is a syndrome associated with multiple complications, high mortality, and subsequent intractable epilepsy. There are multiple causes, some of which are autoimmune encephalitides; however, in this series the majority of patients had no clear etiology identified after extensive evaluation. Prospective studies are needed to determine optimal evaluation and treatment. This study aimed to describe a retrospective, single institution cohort of consecutive adult patients with NORSE with focus on clinical, laboratory, neuroimaging, electroencephalographic features, etiology, treatment, as well as short-term and long-term outcomes. Methods Standard protocol approvals, registrations, and patient consentsThe Johns Hopkins University Institutional Review Board approved this study. Study designWe conducted a retrospective review of all patients with NORSE presenting to The Johns Hopkins Hospital (JHH) in Baltimore, MD, between January 2010 and December 2018. We identified individuals with RSE by review of a continuous video EEG (cEEG) database which included all patients in whom a cEEG of any duration was obtained. Etiology of RSE was determined by neurologists' review of patient charts including clinical notes, laboratory results, neuroimaging studies, and other supporting data.

The timelines of MRI findings related to outcomes in adult patients with new‐onset refractory status epilepticus

“…This retrospective long‐term follow‐up MRI study evaluated the timeline of MRI abnormalities in adult NORSE patients. The percentage of MRI abnormalities in NORSE patients in our study (82%) and other, previous studies (62%‐100%), 2,6–10 was higher than in the general population of SE patients (25%) 11 …”

“…This study demonstrated initial diffuse leptomeningeal enhancement in 43% of NORSE patients, which was higher than in previous studies (6%‐25%) 2,8–10 . The higher percentage can be explained by our different method for calculating the percentage, which used the number of contrast‐enhanced MRIs performed within 16 days of seizure onset, not just the total number of MRIs without consideration for the use of contrast enhancement or the time at which the MRI was performed after seizure onset, as has been described in previous studies.…”

Clinically based score predicting cryptogenic NORSE at the early stage of status epilepticus

“…5 One might argue that C-NORSE is an epileptic syndrome and should not be confused with AE; randomized controlled trial with immunotherapy has not been conducted yet; therefore, little information is available on the adequate dosage of other immune treatments to formulate any recommendation. 3 However, it is not easy in clinical practice to exclude a possibility of C-NORSE or antibody-positive AE particularly at the early stage of SE before antibody test results become available; therefore, many patients with NORSE may have been treated with immunotherapy, 5 , 26 although the first-line immunotherapy is presumed to be less effective. However, if the C-NORSE score is high (≥5) on referral from other hospital, it is suggested that the patient is more likely to be negative for neuronal antibodies, thus more likely to be less responsive to first-line immunotherapy and have poor outcome.…”

How close is ketamine to routine use in refractory status epilepticus?

“…Ketamine, a nonselective and noncompetitive antagonist of NMDAR, blocks the influx of Ca 2+ and Na + by binding to relevant sites inside the ion channel of the NMDAR and consequently inhibiting the transmission of excitatory nerve impulses [7][8][9][10][11]. To understand the efficacy and safety of ketamine in patients with RSE and SRSE, Hofler et al [12] analyzed data from 42 RSE or SRSE patients, and the results showed that 64% of the patients achieved resolution of SE with no adverse events.…”

“…In recent years, ketamine has gradually been used in RSE patients with special etiologies and has achieved good outcomes [7,8]. Anti-NMDAR encephalitis is an autoimmune disease related to the production of antibodies to the NR1 and NR2 subunits of the NMDARs.…”